HUMAN DRUGS

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2-2-0 Labs, Riverside, CA, June 26 (Los Angeles). Deviations from Good Manufacturing Practice (GMP) rules in

the manufacture of over-the-counter (OTC) drugs included inadequate finished product testing of sun screens and other drugs; an unvalidated manufacturing process; deficiencies related to the deionized water system, such as the lack of alert limits for microbial growth, assurance that the water would meet specifications and documentation related to cleaning and maintenance; no documented studies to assure equipment cleaning procedure effectiveness; an unvalidated autoclave; failure to perform routine autoclave maintenance; uncalibrated ovens and temperature monitoring thermometers; and gaps in training. Noting that a number of these observations were similar to pre-vious problems, FDA said it would reinspect the plant. The firm was audited May 21-June 1.

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Abbott Labs, Abbott Park, IL, June 26 (DDMAC). FDA said Abbott sales representatives distributed reprints of articles discussing the use of Depacon (valproate sodium) injection to treat status epilepticus, an unapproved use. The product is indicated for seizures, the agency said. According to the letter, Abbott admitted to providing copies of the articles to regional and district managers, who passed them along to sales representatives. FDA asserted that the sales staff then provided them to health care providers and hospital pharmacists, adding that the studies cited did not seem well-controlled. Terming status epilepticus Aa neurological emergency that has a significant mortality risk,@ FDA stated that this promotion Amay place a vulnerable patient population at great risk.@ In addition, the company had not submitted the reprints in compliance with post-marketing reporting rules, the agency said. Abbott was told to stop us-ing these or any similar items; submit a written statement of intent to comply, along with a list of company personnel who had received the reprints; instruct its staff about lawful promotion; and disseminate a corrective ADear Healthcare Professional@ letter.

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AccuMed, Lawrenceville, NJ, June 9 (New Jersey). The 13-item warning letter cited deviations from GMPs, including the lack of process and cleaning validation protocols and related data for Accumide, Gas Relief Infant Drops, Accuseptic Men-thol Spray and 11 other products; deficiencies in the process validation for Accuotic Ear Drops; a lack of Aestablished hold times for bulk liquid products between manufacturing and filling@; several unqualified manufacturing and packaging equip-ment items; inadequate qualification of a filling line and blender; batch records that contained inconsistencies, incomplete information and correction fluid; inconsistent storage conditions for stability samples; an unqualified high performance liquid chromatography hardware and software system; the failure to investigate an unexplained rejection of Gas Relief Infant Drops and a discrepancy between in-house and contract lab analysis results; inadequate identification of the status of materials in the inventory system; and record-keeping problems. FDA said the company=s response was under review. The facility was in-spected April 23-24, 27-28, May 4 and 7.

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First Priority, Elgin, IL, June 24 (Chicago). GMP deviations included the inadequate control of labeling materials, a lack of written procedures for checking labeling before packaging, use of an unvalidated water system to produce purified water, a lack of bacteriological specifications for water used as a drug component, water leaking from the elbow of a storage tank, re-lease of products before finished product testing was completed, failure of master and batch records to include minimum and maximum theoretical yield specifications, no procedure for quarantining finished product while awaiting testing and a change to the chlorhexidine gluconate formulation without assessing stability. FDA said employees were seen signing records indi-cating that labeling operations were completed before the labels were removed from inventory. Among the products involved were Priority Care Blue Lotion Topical Antiseptic, iodine tincture, isopropyl alcohol, mineral oil, anti-bacterial hand soap, organic iodine, povidone iodine ointment and bismusol. FDA said the company=s response, stating that some standard op-erating procedures (SOPs) had been revised, did not include copies of the procedures. The agency added that the procedures and adherence to them would be verified at the next inspection. The firm was audited April 27-May 5.

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J. Strickland & Company, Memphis, TN, June 17 (Nashville). Black and White Ointment, marketed for Athe tem-porary relief of itching, burning and stinging caused by acne pimples or eczema,@ was declared an unapproved new drug because it was not considered under the review of OTC external analgesics.

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Lohmann Therapy Systems, West Caldwell, NJ, Nov. 5, 1997 (New Jersey). GMP deficiencies in the manufacture of a transdermal nicotine drug product included unvalidated manufacturing process and in-process control systems, incom-plete test method validation, non-adherence to a stability protocol, inadequate data to support in-process hold times and insufficient investigations into assay failures. FDA also found that Lohmann had failed to make seven out of 12 SOP revisions promised after an October 1996 inspection, although the agency acknowledged that the company completed the SOP updates after the more-recent audit. According to the warning letter, Lohmann stated in its reply that Ait is accepted practice for FDA that the validation batch size is smaller than full size commercial lots, as long as the valida-tion batch size is a minimum of 1/10...of the intended commercial batch size, or 100,000 units, whichever is greater.@ The agency disagreed, stating that this amount applied only for filing purposes, with Afull production batches@ required for validation. The company was inspected Sept. 9-Oct. 2, 1997.

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Merck, Whitehouse Station, NJ/West Point, PA, facility, June 16 (Philadelphia). In an eight-page warning letter, FDA said the company=s response to a 483 was inadequate regarding several GMP deviations, including samples that were not assessed annually using all container/closure systems, stopper validation failures involving endotoxin reduction, failure of the quality assurance unit to remove dryers from service despite atypical process reports, and exposure of Prilosec (omeprazole) delayed-release capsules to Apotential debris@ from construction. The warning letter also con-tained a number of questions and suggestions regarding areas such as how FDA wanted Merck to address observations related to batch records, adjustment of the stability specification for phenylethanol content in Decadron Phosphate (dex-amethasone sodium phosphate) ophthalmic solution, a difference between the written response and a verbal reply given at the close of the inspection, interim measures pending reassessment of inspection machines, evaluation of disinfectant procedures, cleaning validation and training. Premarket applications and export approval requests will be withheld un-til the violations are corrected. FDA inspected the facility April 6-May 12.

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MWM, Skokie, IL, June 19 (Chicago). FDA objected to the labeling of PPA (phenylpropanolamine HCl) as an alter-native to prescription obesity treatments, declaring it an unapproved new drug. Misbranding resulted from false and misleading labeling due to the suggestion of safety and effectiveness, which the agency said was not established; the statement that PPA was approved for weight loss by FDA; and an unsubstantiated safety comparison. In addition, PPA, L-Tyrosine, Vitamin C and Vitamin B-6 were deemed misbranded because they improperly carried a prescription legend. The agency also said L-Tyrosine, Vitamin C and Vitamin B6 may be misbranded by claims that they were in-tended to enhance the effectiveness of PPA. The audit occurred March 12-April 1.

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Nature=s Acres, North Freedom, WI, June 30 (Minneapolis). See Cosmetics, page 9.

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Professional Dental Technologies/Pro-Dentec, Batesville, AR, June 22 (Dallas). Pro-Select3 0.12% Chlorhexidine 

Gluconate Irrigation Solution for subgingival irrigation was deemed a new drug because it had no approved application or investigational exemption. The drug was declared adulterated due to false and misleading labeling and misbranded due to labeling deficiencies, inadequate directions for use and failure to list the product with FDA.

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Threshold Enterprises, Scotts Valley, CA, June 24 (San Francisco). Source Naturals Diet-Phen and Ephedra-Free tablets, as well as Horizon Nutraceuticals Slim-Phen and Ephedra-free Slim-Phen tablets, were declared adulterated as unapproved new drugs and misbranded due to false and misleading labeling and a lack of adequate directions for use. FDA objected to labeling that suggested the products were alternatives to the prescription drug phentermine for treating obesity.

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UniGen Pharmaceuticals, Westminster, MD, June 25 (Baltimore). GMP deviations included process validation and equipment qualification deficiencies involving Acetaminophen Children=s Oral Suspension, Quadratuss Pediatric Sus-pension and Guaifenesin NR Liquid; inadequate sampling and testing plans; deficiencies in procedures for calibration, reconciliation of labeling, storage and testing in-process suspensions after long storage periods; a lack of procedures for distribution and complaint handling; insufficient reserve samples; and failure to include minimum and maximum the-oretical yields in master production and control records. Premarket applications and export approval requests will be withheld until the violations are corrected. The audit transpired May 19-27.